It has been demonstrated in this laboratory that corticoid-isoproterenol interaction can consistently elicit severe ventricular dysrhythmias terminating in ventricular fibrillation in the albino rat. This species is otherwise highly resistant to the induction of dysrhythmias by catecholamines. As a result of this interaction with desoxycorticosterone acetate, the acute toxicity of isoproterenol in the rat is increased more than 47,000 times, and with the further addition of aminophylline by 320,000 times. Myocardial sensitization to isoproterenol by corticoid pretreatment is inhibited by the protein synthesis inhibitors such as cycloheximide and actinomycin D. In view of the enormous potentiation brought about by such a drug-drug interaction, which may have played a contributory role in the "death epidemic" among patients with bronchial asthma in the British Commonwealth some years ago, it is proposed (1) to continue the investigation of various combinations of corticosteroids and sympathomimetics for the purpose of determining their comparative propensity for triggering dangerous dysrhythmias and (2) to elucidate the factors in corticosteroid-beta adrenergic agonist interaction which facilitates the emergence of ventricular fibrillation. The investigation will encompass acute and chronic experiments in awake animals (albino rats, dogs and squirrel monkeys), in which blood pressure and ECG may be monitored and which have been pretreated for various periods of time with desoxycorticosterone, hydrocortisone, prednisone, dexamethasone or other adrenal steroids. It is anticipated that the methodology employed may aid in uncovering potentially dangerous cardiotoxia drug-drug interactions and may help in elucidating the mechanisms involved in this phenomenon.